This proposal outlines the development of a general technique to create millions of closely related varients of a monoclonal antibody (mAb). Antibodies of improved affinity could then be found by filter hybridization screening. High affinity mAbs are usually desirable for diagnostic, research and therapeutic applications. The proposed system can also be used cross-species for the conversion of murine mAbs to human mAbs. Murine mAbs are being used in many clinical applications such as cancer, septic shock and transplantation. The use of human mAbs would obviate the human anti-mouse mAb response which often blunts the clinical usefulness of mAb immunotherapy. However, for most indications human mAbs are very difficult or impossible to obtain. Human mAbs made by the proposed method would not have the same antigenic restrictions and thus could be of great practical utility.